Heterologous pathway to produce terpenes
Cells comprising a heterologous metabolic pathway are configured to produce a terpene product containing non-multiples of five carbon, particularly wherein the pathway comprises heterologous Lepidoptera insect juvenile hormone biosynthetic pathway enzymes of the insect's mevalonate pathway.
1. A cell genetically engineered to express a heterologous metabolic pathway comprising heterologous Bombyx mori and/or Choristoneura fumiferana mevalonate pathway enzymes, wherein the cell produces a product of the metabolic pathway that is a C16 terpene, wherein the mevalonate pathway enzymes comprise β-hydroxy β-methylglutaryl-CoA synthase (HMGS), β-hydroxy β-methylglutaryl-CoA reductase (HMGR), mevalonate kinase (MevK), mevalonate phosphate kinase (MevPK), mevalonate pyrophosphate decarboxylase (MevPPD), isopentenyl pyrophosphate isomerase (IPPI) and farnesyl pyrophosphate synthase (FPPS), wherein the metabolic pathway further comprises a terpene cyclase.
2. The cell of claim 1 , wherein the terpene cyclase is Streptomyces coelicolor epi-isozizaene synthase.
3. The cell of claim 1 , wherein the metabolic pathway further comprises propionate-CoA ligase.
4. The cell of claim 1 , wherein the metabolic pathway further comprises S. sativa valeryl-CoA synthase, E. coli FadB and/or Micrococcus luteus Aco.
5. The cell of claim 1 that is E. coli.
6. A method for producing a C16 terpene product, wherein said method comprises growing the cell of claim 1 to produce the product, and isolating or enriching the product.
7. A method of making the cell of claim 1 , wherein said method comprises genetically engineering a cell to comprise a heterologous metabolic pathway comprising a terpene cyclase and heterologous Bombyx mori and/or Choristoneura fumiferana mevalonate pathway enzymes, wherein the mevalonate pathway enzymes comprise β-hydroxy β-methylglutaryl-CoA synthase (HMGS), β-hydroxy β-methylglutaryl-CoA reductase (HMGR), mevalonate kinase (MevK), mevalonate phosphate kinase (MevPK), mevalonate pyrophosphate decarboxylase (MevPPD), isopentenyl pyrophosphate isomerase (IPPI) and farnesyl pyrophosphate synthase (FPPS), and wherein the cell produces a product of the metabolic pathway that is a C16 terpene.